The purpose of the project is to determine if immunologic processes are involved in the pathogenesis of certain problems of human reproduction, namely recurrent abortion and pre-eclampsia, and to learn more of the immune responses of normal pregnancy. Women carrying term pregnancies exhibit lymphocyte reactivity to paternal antigens (production of MIF), which indicates pre-sensitization during pregnancy. Serum collected in late first pregnancy or during and after multiparous pregnancies blocks the release of MIF, and the blocking activity is removed by absorption on an anti-IgG column. The presumed blocked antibodies are not absorbed by pooled platelets with HLA-A,B,C locus antigenic sites, and so far have not shown specificity for paternal B-cells or T-cells. Lymphocyte typing for HLA-A,B,C or Dr locus antigens in maternal-paternal pairs are incomplete. In comparison with multiparous controls, most women with a history of recurrent idiopathic abortion exhibit similar lymphocyte reactvity (MIF) to paternal antigens, but lack serum blocking antibody described above. To date, subjects with pre-eclampsia have not shown evidence of increased cellular immune reactivity or a lack of blocking antibodies. Preliminary results suggest that some subjects have circulating immune complexes present in late pregnancy or after delivery. IgG fractions eluted from term placental tissue can also block autologous lymphocyte reactivity in the MIF assay. Studies are under way to characterize the specificity of placental IgG. Experiments in guinea pigs have not demonstrated that estrogen, progesterone, or crude or purified hCG will block production of MIF by sensitized and stimulated lymphocytes. The macrophage response to MIF was also not blocked by these placental eluates.